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A subgroup analysis of the INPULSIS data shows that nintedanib slowed lung function decline independent of severity of lung function impairment at baseline1

Nintedanib also reduced the proportion of patients with IPF who experienced disease progression as measured by categorical FVC decline2

Nintedanib is the first targeted treatment for IPF to consistently demonstrate its efficacy in two identically designed Phase III trials and this subgroup analysis further underscores its value for IPF patients

Ingelheim, Germany, 9 September 2014 – A pre-specified subgroup analysis from the two replicate Phase III INPULSIS trials, presented today at the European Respiratory Society International Congress (ERS), showed nintedanib slowed disease progression in patients with idiopathic pulmonary fibrosis (IPF), independent of severity of lung function impairment at baseline.1 IPF is a debilitating and fatal lung disease, with a median survival of 2–3 years after diagnosis.3 It causes progressive scarring of the lungs, resulting in continual and irreversible deterioration in lung function and difficulty breathing.4

The pooled analysis of INPULSIS data looked at annual decline in lung function in two pre-specified groups – baseline forced vital capacity (FVC) of >70% (n=700) and ≤70% predicted (n=361). The positive effect of nintedanib on slowing disease progression was similar for both subgroups:1

The results for both subgroups are consistent with the INPULSIS primary endpoint finding for the overall patient population which showed nintedanib, one capsule twice a day, slowed disease progression by reducing the annual rate of decline in lung function by 50% in a broad range of IPF patient types - including patients with early disease (FVC>90% pred), no honeycombing on HRCT and/or concomitant emphysema.5

“Nintedanib is the first targeted treatment for IPF to consistently meet the primary endpoint in two identically designed Phase III trials and this sub-analysis further underscores its efficacy in IPF patients presenting different ranges of lung function impairment at baseline,” said Professor Ulrich Costabel, Ruhrlandklinik University Hospital, Germany.

In a separate, additional analysis of the INPULSIS data, nintedanib* reduced the proportion of patients who experienced disease progression as measured by categorical (absolute or relative) FVC decline.2 A decline in FVC % predicted of >5% and >10% over 6 or 12 months in patients with IPF is a marker of disease progression and associated with reduced survival.3,6,7,8,9,10,11

Results showed:2

In both INPULSIS-1 and 2, significantly more patients taking placebo experienced an absolute decline in predicted FVC of >5%, as well as relative declines of >5% and >10% vs. nintedanib.

In INPULSIS-1, significantly more patients in the placebo group experienced an absolute decline in predicted FVC of >10%; the difference in INPULSIS-2 was numerically in favour of nintedanib* but did not reach statistical significance.

Further pre-specified sensitivity analyses of the INPULSISTM trials presented at the ERS meeting confirm the robustness of the primary and key secondary endpoint results for nintedanib in IPF.12

In both INPULSIS trials, the most common adverse events were gastrointestinal in nature, of mild or moderate intensity, generally manageable and rarely leading to treatment discontinuation.5 The proportion of patients with serious adverse events was similar in all groups.5

“The results of these analyses further confirm and support the efficacy of nintedanib on slowing disease progression in a wide range of patients with IPF,” said Dr Susanne Stowasser, Global Team Leader Medical Affairs, Boehringer Ingelheim. “Boehringer Ingelheim is committed to studying nintedanib further and to making it available to patients with IPF and their treating physicians as soon as possible.”

About the INPULSIS trials
The double blind, randomised and placebo-controlled trials, involving 1,066 patients across 24 countries, evaluated the effect of oral nintedanib* 150 mg twice daily, on the annual rate of decline in forced vital capacity (FVC), in patients with IPF over 52 weeks. The trials had an identical design, matched dosing, inclusion criteria, and endpoints.5,13
The primary endpoint was the annual rate of decline in FVC (expressed in mL over 52 weeks). Key secondary endpoints were: change from baseline in health-related quality of life, as assessed by the Saint-George’s Respiratory Questionnaire (SGRQ) and time to first acute exacerbation. Other secondary endpoints included change from baseline in FVC, overall survival, respiratory mortality, on-treatment survival.5,13

Key results showed:5

nintedanib slows disease progression in IPF by reducing the decline in lung function by 50% compared to patients taking placebo.

there was a significant, albeit small benefit of nintedanib versus placebo in change in SGRQ total score in INPULSIS-2, but no significant difference between groups in INPULSIS-1.

Patients included in the trials were at least 40 years of age, diagnosed with IPF within five years prior to enrolment, based on the most recent American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT) IPF guidelines for diagnosis and management.5,13
Eligibility into the studies was assessed by central review of the high resolution computerised tomography pattern by an expert radiologist and surgical lung biopsy, if available, by an expert pathologist.5,13

About nintedanib
Nintedanib* is an investigational small molecule tyrosine kinase inhibitor (TKI) in development by Boehringer Ingelheim for idiopathic pulmonary fibrosis (IPF).14 Nintedanib*, only one capsule twice a day, slows disease progression by reducing the annual rate of decline in lung function by 50% in a broad range of IPF patient types - including patients with early disease (FVC>90% pred), no honeycombing on HRCT and/or concomitant emphysema.5 Only nintedanib* reduces adjudicated acute exacerbations□ by 68%.5 This can be crucial given that approximately 50% of patients hospitalised for an acute IPF exacerbation die during hospitalisation.15 Side-effects with nintedanib* can be effectively managed in most patients.5

Nintedanib targets growth factor receptors, which have been shown to be potentially involved in pathomechanisms of pulmonary fibrosis, most importantly the platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).14,16,17 By blocking the signaling pathways that are involved in fibrotic processes, it is believed that nintedanib has the potential to reduce disease progression in IPF by slowing the decline of lung function.14,16,18 Nintedanib is also in clinical development as a treatment option for cancer, including non-small cell lung cancer, ovarian cancer, colorectal cancer and hepatocellular carcinoma.

About idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, severely debilitating and ultimately lethal lung disease for which there are limited treatment options.3 IPF affects as many as 14–43 people per 100,000 worldwide.19,20 IPF is characterised by progressive scarring of lung tissue and loss of lung function over time.16,21 Development of scarred tissue is called fibrosis.3 Over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream, and vital organs do not get enough oxygen.4 As a result, individuals with IPF experience shortness of breath, cough and often have difficulty participating in everyday physical activities.22

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative “Making more Health” and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2013, Boehringer Ingelheim achieved net sales of about €14.1 billion. R&D expenditure corresponds to 19.5% of its net sales.

Footnotes

*Nintedanib is an investigational compound. Its safety and efficacy have not yet been fully established.‡Categorical declines in FVC % predicted can be measured as absolute or relative declines·

e.g. 60% to 50% predicted is a 10% absolute decline

e.g. 60% to 54% predicted is a 10% relative decline

(Richeldi L, etal. Thorax 2012;67:407–11)

□Adjudicated exacerbations’ was a pre-specified sensitivity analysis in the pooled data set. Time to first Investigator-reported exacerbation was a secondary endpoint which was met in TOMORROW and INPULSIS™-2 but not in INPULSIS-1